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Secondary structure of DNA: Epigenetic regulation and resolution by helicases
Par Phong Lan Thao TRAN (Regulation et Dynamique des Genomes, Muséum)
Le 28 Novembre 2017 à 11h00 - Salle de séminaires 5ème étage, Tour 32-33


Guanine quadruplexes (G4) are non-canonical four-stranded nucleic acid structures formed by guanine-rich DNA and RNA sequences. G4 motifs, which are commonly found in gene promoters, replication origins, and DNA telomeric regions, as well as in RNA, are strongly suspected to be implicated in the regulation of DNA replication, transcription and translation in vivo. My PhD research contributed to the study of the formation of G4 structures using biophysical and biochemical approaches, and to the development of a high throughput G4-ligand screening method allowing the comparison of interactions between G4-ligands and different G4-DNA/RNA biological sequences. I also employed the DNA origami technique to build up a DNA nanostructure and observe G4 formation at the single-molecule level.

It was shown recently that G4-forming sequences at gene promoters (e.g. proto-oncogenes) can serve as sensors of oxidative stress. In particular, 8-oxoguanine (OG) is an important oxidation-induced modification of guanine. Sensitive assays to follow OG deposition in DNA are therefore needed to better understand OG biological and medical significance. My current project in the Boulé lab aims to characterize the dynamics of OG deposition in DNA in a cellular context, and in parallel study the effect of OG on DNA biophysical properties (e.g. G4 formation) and thermodynamics, and on its interaction with proteins (e.g. helicases).

Pif1-family helicases can resolve G4 structures in vitro and are involved in promoting replication fork progression through G4 sequences. My postdoctoral research in the Zakian lab at Princeton University identified a new role of Pif1-family helicases in suppressing DNA damage at genes coding for transfer RNA.